The goal of this project is to identify and understand the function of the proteins involved in mitosis and cell division using the simple eukaryote Aspergillus nidulans as a model system. We have initiated a combined morphological, biochemical and genetic study of mutants of A. nidulans which are either temperature-sensitive for mitosis or cell division or are altered in their sensitivity to one or more antimitotic drugs. A number of such mutants have been characterized in this and other laboratories and these are available to us for study. We have recently discovered that mutants of A. nidulans resistant to the antimitotic fungicide benomyl because of a mutation in the benA gene have abnormal beta-tubulins, and we have identified benA as a structural gene for beta-tubulin in Aspergillus. Special attention will be given to the biochemical analysis of the mutant beta-tubulins of the benA mutants. The altered peptides and amino acids of the mutant beta-tubulins will be located and identified in order to characterize the amino acid determinants of benomyl binding to beta-tubulin. The eventual result to these experiments will be a molecular map of the benomyl binding site. Since benomyl inhibits tubulin polymerization, these studies may provide important information about the structural biochemistry of microtubule polymerization.